p63(TP63) elicits strong trans-activation of the MFG-E8/lactadherin/BA46 gene through interactions between the TA and DeltaN isoforms.

p63(TP63) elicits strong trans-activation of the MFG-E8/lactadherin/BA46 gene through interactions between the TA and DeltaN isoforms. Research Abstract Details 

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p63(TP63) elicits strong trans-activation of the MFG-E8/lactadherin/BA46 gene through interactions between the TA and DeltaN isoforms. Abstract Text:

T Okuyama,S Kurata,Y Tomimori,N Fukunishi,S Sato,M Osada,K Tsukinoki,H-F Jin,A Yamashita,M Ito,S Kobayashi,R-I Hata,Y Ikawa,I Katoh,T Okuyama,S Kurata,Y Tomimori,N Fukunishi,S Sato,M Osada,K Tsukinoki,H-F Jin,A Yamashita,M Ito,S Kobayashi,R-I Hata,Y Ikawa,I Katoh,

We report here that human MFGE8 encoding milk fat globule-EGF factor 8 protein (MFG-E8), also termed 46 kDa breast epithelial antigen and lactadherin, is transcriptionally activated by p63, or TP63, a p53 (TP53) family protein frequently overexpressed in head-and-neck squamous cell carcinomas, mammary carcinomas and so on. Despite that human MFG-E8 was originally identified as a breast cancer marker, and has recently been reported to provide peptides for cancer immunotherapy, its transcriptional control remains an open question. Observations in immunohistochemical analyses, a tetracycline-induced p63 expression system and keratinocyte cultures suggested a physiological link between p63 and MFGE8. By reporter assays with immediately upstream regions of MFGE8, we determined that the trans-activator (TA) isoforms of p63 activate MFGE8 transcription though a p53/p63 motif at -370, which was confirmed by a chromatin immunoprecipitation experiment. Upon siRNA-mediated p63 silencing in a squamous cell carinoma line, MFG-E8 production decreased to diminish Saos-2 cell adhesion. Interestingly, the DeltaN-p63 isoform lacking the TA domain enhanced the MFGE8-activating function of TA-p63, if DeltaN-p63 was dominant over TA-p63 as typically observed in undifferentiated keratinocytes and squamous cell carcinomas, implying a self-regulatory mechanism of p63 by the TA:DeltaN association. MFG-E8 may provide a novel pathway of epithelial-nonepithelial cell interactions inducible by p63, probably in pathological processes.

p63(TP63) elicits strong trans-activation of the MFG-E8/lactadherin/BA46 gene through interactions between the TA and DeltaN isoforms. Publishing Authors By Initials

T Okuyama,S Kurata,Y Tomimori,N Fukunishi,S Sato,M Osada,K Tsukinoki,HF Jin,A Yamashita,M Ito,S Kobayashi,RI Hata,Y Ikawa,I Katoh,T Okuyama,S Kurata,Y Tomimori,N Fukunishi,S Sato,M Osada,K Tsukinoki,HF Jin,A Yamashita,M Ito,S Kobayashi,RI Hata,Y Ikawa,I Katoh,

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p63(TP63) elicits strong trans-activation of the MFG-E8/lactadherin/BA46 gene through interactions between the TA and DeltaN isoforms. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Oncogene

VOLUME: 27

Page Numbers: 308-17

Journal Abbreviation: Oncogene

ISSN: 1476-5594

DAY: 16

MONTH: 07

YEAR: 2007

p63(TP63) elicits strong trans-activation of the MFG-E8/lactadherin/BA46 gene through interactions between the TA and DeltaN isoforms. Information

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LANGUAGE: eng

NlmUniqueID: 8711562

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Grant and Affiliation Information for p63(TP63) elicits strong trans-activation of the MFG-E8/lactadherin/BA46 gene through interactions between the TA and DeltaN isoforms.

AFFILIATION: Ikawa Laboratory, RIKEN, Wako, Japan.

Country: England

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MEDLINETA: Oncogene

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• p63(TP63) elicits strong trans-activation of the MFG-E8/lactadherin/BA46 gene through interactions between the TA and DeltaN isoforms.